Summary This proposal requests R13 support for a longstanding, well-attended, and well-received Gordon Research Conference (GRC) on Excitatory Synapses and Brain Function on June 9-14, 2019 at University of New England, Biddeford ME. The GRC will be preceded by a Gordon Research Seminar (GRS) targeted towards graduate students and postdoctoral fellows on June 8, 9 2019 at the same location. The synapse is central to our understanding of brain function and behavior. In the central nervous system, excitatory synapses represent the primary means of information processing by local circuits and communication between brain regions and thus serve to mediate sensory processing, motor control, cognition and behavior. Importantly, synapses serve as the site of action for many commonly prescribed medications and synaptic dysfunction contributes to many neurological and psychiatric disorders. These include schizophrenia, autism, depression, drug addiction, Parkinson's disease, Alzheimer's disease, traumatic brain injury, stroke and epilepsy. In some cases, synaptic dysfunction is causal in disease, whereas in other cases it represents the downstream sequelae of one or more underlying molecular defects. Thus, therapeutic strategies for these diseases are targeted to modify, repair or maintain synaptic function. Therefore, a fundamental understanding of synapse development, structure, molecular organization, signaling function, and plasticity in both the healthy and diseased brain is essential to lessening the burden of human neurological disease and predicting and improving mental health. This conference is unique in its focus on excitatory synapses, the major synapse type in the brain, and in its multidisciplinary group of participants including structural biologists, molecular and developmental biologists, cell biologists, biochemists, biophysicists, neurophysiologists and systems neuroscientists. The conference is intended to relate fundamental insights in excitatory synaptic function to the impairments in synaptic function that occur in neurological disease, as well as the maladaptive plasticity that contributes to drug addiction. The goal of the conference is to identify and highlight fundamental new insights into synaptic function and dysfunction from a thematic approach. The program has been designed to also highlight cutting edge approaches and to stimulate new concepts, methods and technologies within a sound biological framework of fundamental neuroscience. The conference will bring together expert scientists worldwide in an environment that is conducive to discussion and exchange of ideas. The exchange of ideas at this conference has been a driving force for the field. We expect the 2019 GRC on Excitatory Synapses and Brain Function will shape future scientific directions and provide critical support for the mission of NINDS as well as other NIH institutes such as NIMH, NIDA and NIA.